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US08906681B2 Reliable stabilization of N-linked polypeptide native states with enhanced aromatic sequons located in polypeptide tight turns 有权
N链多肽天然状态的可靠稳定与位于多肽紧密转弯中的增强的芳香族序列

Reliable stabilization of N-linked polypeptide native states with enhanced aromatic sequons located in polypeptide tight turns
Abstract:
A chimeric therapeutic polypeptide of a pre-existing therapeutic polypeptide is disclosed, as are a method of enhancing folded stabilization and a pharmaceutical composition of the glycosylated chimer. The pre-existing and chimeric polypeptides have substantially the same length, substantially the same amino acid residue sequence, and exhibit at least one tight turn containing a sequence of four to about seven amino acid residues in which at least two amino acid side chains extend on the same side of the tight turn and are within less than about 7 Å of each other. The chimeric therapeutic polypeptide has the sequon Aro-(Xxx)n-(Zzz)p-Asn-Yyy-Thr/Ser (SEQ ID NO:001) within that tight turn sequence such that the side chains of the Aro, Asn and Thr/Ser amino acid residues project on the same side of the turn and are within less than about 7 Å of each other. That sequon is absent from the pre-existing therapeutic polypeptide.
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